Frequently asked questions - Clinical trials
Access to unapproved therapeutic goods
Who can sponsor a clinical trial?
Clinical trials can be sponsored by individuals (eg medical practitioners), bodies and organisations (eg hospital, Area Health Service, non-government organisations) or companies (eg pharmaceutical companies). The type of sponsor will vary from trial to trial, depending on who takes overall responsibility for the conduct of the trial. The sponsor usually initiates, organises and supports a clinical study and carries the medico-legal responsibility associated with the conduct of the trial. If the investigator initiates and organises the trial, he or she is to be defined as the sponsor of the trial and will be responsible for the sponsor's functions. This includes where another party (usually a pharmaceutical company) provides the medicinal product used in the clinical trial but has no other involvement in the conduct of the trial.
In signing up as the sponsor of a trial, what are my responsibilities?
The general responsibilities of sponsors of clinical trials are set out in section 5 of the CPMP/ICH Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) <http://www.tga.gov.au/docs/html/ich13595.htm>. The sponsor must also fulfil all regulatory requirements of the TGA and comply with State and Territory legislation in relation to the supply of therapeutic goods.
The sponsor is also responsible for establishing legal and financial agreements between the sponsor, investigators and participating institutions/organisations. These should address issues such as indemnity of the parties involved in the trial and compensation and treatment of trial participants in the case of injury or death.
Does the sponsor of a clinical trial in Australia have to be an Australian entity?
Yes.
When do I need to notify a trial to the TGA?
A notification under the CTN Scheme (or application under the CTX Scheme) is required for all clinical investigational use of a product in Australia, where that use involves:
- a product not entered on the Australian Register of Therapeutic Goods, including any new formulation of an existing product or any new route of administration; or
- use of a registered or listed product outside the conditions of its marketing approval.
It is important to distinguish between clinical trials and use of a product in an individual patient as part of clinical practice. Use of unapproved products in individual patients as part of clinical patient care should be done using the provisions of the Special Access or Authorised Prescriber Scheme and not as a clinical trial. Use of approved products outside the conditions of marketing approval (so called 'off label' use) is legal when done by medical practitioners for individual patients. They do not require Special Access Scheme approval.
A clinical trial should always have a specific aim that addresses a scientific question. The trial should be designed to collect the information necessary to provide evidence in answer the question posed and should therefore advance scientific knowledge.
Clinical trials in which products are used within the conditions of their marketing approval are not subject to CTN or CTX requirements but will still need to be approved by an Human Research Ethics Committee (HREC) before the trial may commence.
I've sent in a CTN form. Do I have to wait for TGA acknowledgment before I can start the trial?
The CTN Scheme is a notification scheme and, as such, no TGA approval is given. A clinical trial is deemed to have been notified as soon as the requirements set out under Item 3 of Schedule 5A of the Regulations have been met (ie completion of the CTN form and forwarding it and the relevant fee to the TGA). Once this occurs the exemption under Section 18(1) comes into effect and the sponsor can supply the goods. Thus, legally, a sponsor does not have to wait for the TGA's acknowledgment letter before commencing the trial. However, it may be advisable for sponsors to wait for the TGA's acknowledgment in case there is anything, such as incomplete information on the CTN form that might invalidate the notification.
What are the TGA costs related to clinical trials?
The costs for applications for clinical trials under the CTX scheme cost more than notifications under the CTN. This reflects the increased work required by TGA to evaluate the data provided. There is a single fee for the CTX that includes both Parts 1 and 2.
For the CTN there is a notification fee. It is preferred if all sites participating in the trial are notified either simultaneously or in groups. This is reflected in the current fee structure for the CTN Scheme:
| All sites notified at same time: (including composite sites) |
single notification fee |
|---|---|
| Each site notified singly: | notification fee for each separate notification |
| Sites notified in groups: | notification fee for notification of each group |
The current fees for clinical trials are available from this website <http://www.tga.gov.au/docs/html/feesach.htm>.
It is important to appreciate that TGA cannot treat subgroups of triallists differently according to their ability to pay.
Do we need to notify the TGA of protocol amendments?
The TGA does not require protocol amendments to be notified by sponsors where the amendments seek to clarify the use of, and/or monitoring of treatment. However if there is a major change to the protocol such as the addition of new products or a major change in the conduct of the trial such that the ethics committees require a change to the conditions of their approval a new notification to the TGA may be required.
When is a new CTN form required?
A new CTN is required in the following circumstances where an existing CTN for the trial has been sent:
- There is a significant change in the protocol that resulted in a change in the HREC approval or conditions of the approval. The new notification should indicate to the TGA that the ethics committee at each site has approved the amended protocol.
- There is any additional new unapproved therapeutic products being added to the trial. The HREC approval should indicate that each institution at which the trial is being conducted has approved the additional investigational therapy.
If there is any doubt as to whether a new notification is required then advice should be sought from the TGA.
Can any HREC approve a clinical trial?
Clinical trials involving the use of therapeutic goods that require an exemption under the Therapeutic Goods Act 1989 must be approved by ethics committees that are constituted and operating in accordance with the NHMRC's National Statement on Ethical Conduct in Research Involving Humans. With respect to the conduct of a trial at a specific site, approval of the trial is required from an ethics committee with jurisdiction at that site.
Should a witness be present during the informed consent process?
Advice about obtaining informed consent can be sought from either the ethics committee that has approved the trial protocol or the NHMRC National Statement on Ethical Conduct in Human Research - 2007. Additional advice for investigators on this matter can be found in the section 4 of the CPMP/ICH Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) <http://www.tga.gov.au/docs/html/ich13595.htm>.
Do I have to notify the TGA of the use of a placebo arm in a clinical trial of a registered medicine used for its registered indication?
No. Although presented as though it were a therapeutic good, the placebo has no use in alleviating or curing a disease and its use is for the purpose of assessing the efficacy or safety of the test drug. If there is no other reason to notify a clinical trial, the use of a placebo does not require notification.